Why Heart Attack Triggers Arrhythmia in Some Patients

By staff

US Pharm. 2019;44(2):HS-6-HS-8.

A research team led by the University of California San Diego (UCSD) identified a genetic pathway that causes some people to develop an arrhythmia after a heart attack. They have also found a drug candidate that can block this pathway. The team reported their findings in a study published recently in Nature Biomedical Engineering.

“We now know one reason why a significant fraction of the public could develop secondary complications post heart attack, like an arrhythmia,” said Adam Engler, a bioengineering professor at the UCSD Jacobs School of Engineering. “We have identified the adverse reactions that cause this comorbidity in certain patients and can begin to develop drugs to treat and prevent it.”

This pathway from heart attack to arrhythmia, the scientists uncovered, is triggered by genetic mutations located in a region of the genome called the 9p21locus. These mutations are present in about 23% of the population.

Engler and his colleagues discovered that when a heart attack hits, the mutations activate a signaling protein called JNK. Normal heart cells can keep JNK in check after a heart attack. In cells with the mutations, however, JNK sends signals to downstream targets that disrupt electrical connections between heart cells and cause them to beat out of sync.

The researchers also showed they could reverse and prevent this damage by blocking JNK using a molecule called SP600125, a known JNK inhibitor. According to Engler, JNK derivatives have not been tested clinically for cardiac conditions associated with 9p21 because they may have off-target effects.

“In the future, we envision that cardiac patients could have their genomes sequenced, and if they have the 9p21 mutations, they could be given a drug based on this inhibitor so they are better off in the event of a heart attack and won’t develop arrhythmia,” predicted Engler.